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Pulmonary drug delivery

Xiaobo Wang, Yinan Wang, Ronggang Xi, Yuanyuan Wang, Xiaobo Yang
The optimization of process parameters of spray-dried powder containing fanhuncaoin, a newly discovered antiinflammatorily active phenolic acid isolated from Chinese herb, was conducted using response surface methodology (RSM). The experimental results were fitted into partial cubic polynomial model to describe and predict the response quality in terms of the final angle of repose, aerodynamic diameter, respirable fraction (RF) and yield. The recommended optimum spray-drying parameters for development of fanhuncaoin powder with optimum quality were 110 °C inlet temperature, 0...
March 15, 2018: Drug Development and Industrial Pharmacy
Noor Hafizah Arbain, Norazlinaliza Salim, Hamid Reza Fard Masoumi, Tin Wui Wong, Mahiran Basri, Mohd Basyaruddin Abdul Rahman
Bioavailability of quercetin, a flavonoid potentially known to combat cancer, is challenging due to hydrophobic nature. Oil-in-water (O/W) nanoemulsion system could be used as nanocarrier for quercertin to be delivered to lung via pulmonary delivery. The novelty of this nanoformulation was introduced by using palm oil ester/ricinoleic acid as oil phase which formed spherical shape nanoemulsion as measured by transmission electron microscopy and Zetasizer analyses. High energy emulsification method and D-optimal mixture design were used to optimize the composition towards the volume median diameter...
March 14, 2018: Drug Delivery and Translational Research
Ziyu Zhao, Zhengwei Huang, Xuejuan Zhang, Ying Huang, Yingtong Cui, Cheng Ma, Guanlin Wang, Tim Freeman, Xiang-Yun Lu, Xin Pan, Chuanbin Wu
BACKGROUND: The hygroscopicity of raffinose carrier for dry powder inhaler (DPI) was the main obstacle for its further application. Hygroscopicity-induced agglomeration would cause deterioration of aerosolization performance of raffinose, undermining the delivery efficiency. METHODS: Cyclodextrin-raffinose binary carriers (CRBCs) were produced by spray-drying so as to surmount the above issue. Physicochemical attributes and formation mechanism of CRBCs were explored in detail...
March 13, 2018: Expert Opinion on Drug Delivery
Charlotte H Maden, David Fairman, Michelle Chalker, Maria J Costa, William A Fahy, Nadia Garman, Pauline T Lukey, Tim Mant, Simon Parry, Juliet K Simpson, Robert J Slack, Stuart Kendrick, Richard P Marshall
PURPOSE: Inhaled drug delivery is an attractive route by which to deliver drugs to lungs of patients with idiopathic pulmonary fibrosis (IPF). GSK3008348 is a potent and selective small molecule being developed as the first inhaled inhibitor of the αvβ6 integrin for the treatment of IPF. The phase 1 first-time-in-human clinical trial (NCT02612051) presented here was designed to investigate the safety, tolerability and pharmacokinetic (PK) profile of single doses of GSK3008348 in healthy participants...
March 12, 2018: European Journal of Clinical Pharmacology
Jahidur Rashid, Kamrun Nahar, Snehal Raut, Ali Keshavarz, Fakhrul Ahsan
We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long acting nitric oxide donorboth loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC)in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified- and CAR-modified-liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia induced PAH rats...
March 12, 2018: Molecular Pharmaceutics
Suoyuan Li, Tao Zhang, Weiguo Xu, Jianxun Ding, Fei Yin, Jing Xu, Wei Sun, Hongsheng Wang, Mengxiong Sun, Zhengdong Cai, Yingqi Hua
PURPOSE: Osteosarcoma is the most common primary bone cancer and is notorious for pulmonary metastasis, representing a major threat to pediatric patients. An effective drug targeting osteosarcoma and its lung metastasis is urgently needed. DESIGN: In this study, a sarcoma-targeting peptide-decorated disulfide-crosslinked polypeptide nanogel (STP-NG) was exploited for enhanced intracellular delivery of shikonin (SHK), an extract of a medicinal herb, to inhibit osteosarcoma progression with minimal systemic toxicity...
2018: Theranostics
Kenny Schlosser, Mohamad Taha, Duncan J Stewart
There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV ) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A)...
2018: Theranostics
Arul Prakash Francis, Thiyagarajan Devasena
Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose...
January 1, 2018: Toxicology and Industrial Health
Gergely Hetényi, Janine Griesser, Simon Fontana, Anja Martinez Gutierrez, Helmut Ellemunter, Katharina Niedermayr, Péter Szabó, Andreas Bernkop-Schnürch
AIM: The aim of the study was to develop self-emulsifying delivery systems (SEDDS) exhibiting improved permeation rate for pulmonary delivery of amikacin for treatment of cystic fibrosis (CF) patients. MATERIALS & METHODS: Solubility of amikacin in lipids was improved by hydrophobic ion pairing with sodium myristyl sulfate. The complex was loaded into SEDDS. Drug-release studies were performed and the permeation properties of SEDDS through human CF mucus were examined...
February 28, 2018: Nanomedicine
Kamal Dua, Rajendra Awasthi, Jyotsana R Madan, Dinesh K Chellappan, Buchi N Nalluri, Gaurav Gupta, Mary Bebawy, Philip M Hansbro
No abstract text is available yet for this article.
February 26, 2018: Panminerva Medica
Arcadia Woods, Khondaker Miraz Rahman
Inhaled antimicrobials have been extremely beneficial in treating respiratory infections, particularly chronic infections in a lung with cystic fibrosis. The pulmonary delivery of antibiotics has been demonstrated to improve treatment efficacy, reduce systemic side effects and, critically, reduce drug exposure to commensal bacteria compared with systemic administration, reducing selective pressure for antimicrobial resistance. This review will explore the specific challenges of pulmonary delivery of a number of differing antimicrobial molecules, and the formulation and technological approaches that have been used to overcome these difficulties...
February 23, 2018: Future Medicinal Chemistry
Maliheh Ghadiri, Finbarr Canney, Cristina Pacciana, Gaia Colombo, Paul M Young, Daniela Traini
A limitation in the systemic uptake of many inhalable drugs is the restricted permeation through the pulmonary epithelial layer barrier. One strategy to bypass the epithelial layer when delivering non-permeable drugs is to alter the paracellular transport, allowing the uptake of drugs into the systemic circulation. In this study, the potential of sodium decanoate (Na dec), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as absorption enhancers has been investigated to increase pulmonary paracellular permeability by modulating epithelial cells' tight junctions...
February 16, 2018: International Journal of Pharmaceutics
Warren M Zapol, H Cecil Charles, Andrew R Martin, Rui C Sá, Binglan Yu, Fumito Ichinose, Neil MacIntyre, Joseph Mammarappallil, Richard Moon, John Z Chen, Eric T Geier, Chantal Darquenne, G Kim Prisk, Ira Katz
The 21st Congress for the International Society for Aerosols in Medicine included, for the first time, a session on Pulmonary Delivery of Therapeutic and Diagnostic Gases. The rationale for such a session within ISAM is that the pulmonary delivery of gaseous drugs in many cases targets the same therapeutic areas as aerosol drug delivery, and is in many scientific and technical aspects similar to aerosol drug delivery. This article serves as a report on the recent ISAM congress session providing a synopsis of each of the presentations...
February 16, 2018: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Mona G Arafa, Bassam M Ayoub
No abstract text is available yet for this article.
February 16, 2018: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Nadine Schaefer, Ann-Katrin Kroll, Matthias W Laschke, Michael D Menger, Hans H Maurer, Markus R Meyer, Peter H Schmidt
BACKGROUND: Since their appearance on the drugs of abuse market, synthetic cannabinoids (SCs) are gaining increasing toxicological relevance. They are consumed without knowledge of their toxicokinetic (TK) and toxicodynamic properties and human studies are not allowed due to ethical reasons. A controlled animal TK study following nebulization of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone (RCS-4) as well as Δ9-tetrahydrocannabinol (THC) to pigs should be helpful for better interpretation of analytical results in cases of misuse or poisoning...
February 14, 2018: Current Drug Delivery
Gokce Alp, Nihal Aydogan
Effective and efficient spreading of drug formulations on the pulmonary mucosal layer is key to successful delivery of therapeutics through the lungs. Pulmonary mucus layer, which covers the airway surface, acts as a barrier against therapeutic agents, especially in the case of chronic lung diseases due to increased thickness and viscosity of mucus. Therefore, spreading of the drug formulations on the airways gets harder. Although spreading experiments have been conducted with different types of formulations on mucus-mimicking subphases, a highly effective formulation is yet to be discovered...
February 13, 2018: Molecular Pharmaceutics
Longfa Kou, Yangzom D Bhutia, Qing Yao, Zhonggui He, Jin Sun, Vadivel Ganapathy
Targeted nano-drug delivery systems conjugated with specific ligands to target selective cell-surface receptors or transporters could enhance the efficacy of drug delivery and therapy. Transporters are expressed differentially on the cell-surface of different cell types, and also specific transporters are expressed at higher than normal levels in selective cell types under pathological conditions. They also play a key role in intestinal absorption, delivery via non-oral routes (e.g., pulmonary route and nasal route), and transfer across biological barriers (e...
2018: Frontiers in Pharmacology
Duy-Khiet Ho, Ana Costa, Chiara De Rossi, Cristiane de Souza Carvalho-Wodarz, Brigitta Loretz, Claus-Michael Lehr
The majority of the currently used and developed anti-infectives are poorly water-soluble molecules. The poor solubility might lead to limited bioavailability and pharmacological action of the drug. Novel pharmaceutical materials have thus been designed to solve those problems and improve drug delivery. In this study, we propose a facile method to produce sub-microcarriers (sMCs) by electrostatic gelation of anionic ß-Cyclodextrin (aß-CD) and chitosan. The average hydrodynamic size ranged from 400-900 nm by carefully adjusting polymer concentrations and N/C ratio...
February 9, 2018: Molecular Pharmaceutics
Sarah J Nevitt, Judith Thornton, Clare S Murray, Tiffany Dwyer
BACKGROUND: Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe...
February 9, 2018: Cochrane Database of Systematic Reviews
Hamed Vakilzadeh, Jaleh Varshosaz, Mohsen Minaiyan
INTRODUCTION: Triptorelin the synthetic analog of gonadotrophin-releasing hormone is used for treatment of sex hormone dependent diseases via parenteral administration. The aim of the present study was investigation the possibility of triptorelin pulmonary delivery and preparation of a pulmonary nanocarrier delivery system for it. METHODS: Triptorelin was loaded in Pluronic-F127 grafted poly (methyl vinyl ether-alt-maleic acid) nanomicelles by direct dissolution method...
February 8, 2018: Current Drug Delivery
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